Resolvins and inflammatory pain

Resolvins are a group of molecules derived from omega-3 fatty acids. They are part of a biochemical program that allows inflamed tissues to return to homeostasis once the need for the inflammatory response is over. Resolvins act in very low dose ranges in vitro and in vivo. New data suggest that they might have the potential to become very potent analgesic drugs in inflammatory pain

Analyzing marker substances for Complex Regional Pain Syndrome (CRPS)

Weniger als 5% der Patienten entwickeln Komplex-Regionales Schmerzsyndrom (CRPS) nach einem Trauma, insbesondere nach Frakturen. Es ist ein schmerzhaftes Syndrom, dass durch eine Vielzahl von klinischen Merkmalen gekennzeichnet ist. Es kann chronisch werden, wenn es nicht in den ersten Monaten kuriert wird. Wahrscheinlich spielen mehrere pathophysiologische Mechanismen eine Rolle in CRPS. Es wird vermutet, dass Neuropeptide und anti-inflammatorische Lipid-Mediatoren involviert sind. In dieser Arbeit wurden diese Moleküle in Hautbiopsien und Serum mit dem Ziel der Korrelation ihrer Konzentration mit klinischen Parametern mittels Massenspektrometrie (MS) untersucht. Hochauflösende und insbesondere NanoMS identifizierte Peptide und Fettsäuren im niederen fmol-Bereich. Die Methodik zeigte aber auch wenig Toleranz gegenüber dem chemischen Untergrund, so dass vornehmlich die robustere Kapillarchromatography eingesetzt wurde. Die Serum-Proteaseaktivität mit einem Fokus auf Angiotensin-konvertierendem Enzym (ACE) wurde untersucht. Bradykinin (BK) wurde zügig zu BK1-8 und BK1-5 abgebaut. Niedrigere BK1-5 Levels waren in Übereinstimmung mit der Hypothese verringerter ACE-Aktivität in CRPS.Less than 5% of patients develop Complex Regional Pain Syndrome (CRPS) after trauma, mostly after fractures. It is a painful syndrome characterized by a variety of clinical features including classical signs of inflammation and it can become chronical if not cured in the first few months. Likely, a number of pathophysiological mechanisms play a role in CRPS. The involvement of neuropeptides and anti-inflammatory lipid mediators has been suggested. Here, mass spectrometry (MS) was used to investigate these molecules in skin biopsies and serum with the aim of correlating their concentration with clinical parameters. High-end and in particular nanoscale MS identified peptides as well as fatty acids at the low fmol level. However, it also showed little tolerance for the chemical background so that a more robust capillary chromatography approach was preferentially used. Serum protease activity with a focus on angiotensin converting enzyme (ACE) was studied. Bradykinin (BK) was rapidly degraded to BK1-8 and BK1-5. The formation of lower BK1-5 levels was indicated in agreement with the hypothesis of reduced ACE-activity in CRPS

Standards for the diagnosis and management of Complex Regional Pain Syndrome: Results of a European Pain Federation task force

Background: Complex Regional Pain Syndrome is a painful and disabling post-traumatic primary pain disorder. Acute and chronic CRPS are major clinical challenges. In Europe progress is hampered by significant heterogeneity in clinical practice. We sought to establish standards for the diagnosis and management of CPRS. Methods: The European Pain Federation established a pan-European task force of experts in CRPS who followed a four-stage consensus challenge process to produce mandatory quality standards worded as grammatically imperative (must-do) statements. Results: We developed 17 standards in 8 areas of care. There are 2 standards in diagnosis, 1 in multi-disciplinary care, 1 on assessment, 3 for care pathways, 1 on information and education, 4 in pain management, 3 in physical rehabilitation, and 2 on distress management. The standards are presented, summarised, and their generation and consequences discussed. Also presented are domains of practice for which no agreement on a standard could be reached. Areas of research needed to improve the validity and uptake of these standards are discussed. Conclusion: The European Pain Federation task force present 17 standards of the diagnosis and management of CPRS for use in Europe. These are considered achievable for most countries, and aspirational for a minority of countries depending on their healthcare resource and structures.Significance: This position statement summarizes expert opinion on acceptable standards for CRPS care in Europe

microRNAs in nociceptive circuits as predictors of future clinical applications

Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs - and microRNAs (miRNAs) in particular - regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesized as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioral components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals. \ua9 2013 Kress, H\ufcttenhofer, Landry, Kuner, Favereaux, Greenberg, Bednarik, Heppenstall, Kronenberg, Malcangio, Rittner, c\ue7eyler, Trajanoski, Mouritzen, Birklein, Sommer and Soreq

Global series: Complex regional pain syndrome: abstracts from the International Association for the Study of Pain complex regional pain syndrome SIG virtual symposia 2021

The aim of this IASP complex regional pain syndrome (CRPS) SIG Global Series 2021 was to bring together clinicians including those from developing countries to better understand the clinical presentation of complex regional pain syndrome in countries with less well-published patient populations. The purpose was to learn from each other about the range of treatments, successful outcomes, and challenges experienced. These meeting proceedings comprise abstracts from nine countries that span 4 continents and are summaries of online presentations delivered by speakers representing these countries over the course of 2 symposia. The symposia were attended by a global audience of approximately 360 people. Patients with CRPS were described and treated by clinicians from countries across Asia (Pakistan, Jordan, South Korea, Taiwan, and Singapore), South America (Brazil and Peru), Africa (South Africa), and Europe (Norway). This reflects that CRPS exists across borders, ethnicities, and cultures. These proceedings provide a broader perspective within the international pain community about how we can better understand and treat CRPS across the globe

Thermography imaging during static and controlled thermoregulation in complex regional pain syndrome type 1: diagnostic value and involvement of the central sympathetic system

BACKGROUND: Complex Regional Pain Syndrome type 1 (CRPS1) is a clinical diagnosis based on criteria describing symptoms of the disease. The main aim of the present study was to compare the sensitivity and specificity of calculation methods used to assess thermographic images (infrared imaging) obtained during temperature provocation. The secondary objective was to obtain information about the involvement of the sympathetic system in CRPS1. METHODS: We studied 12 patients in whom CRPS1 was diagnosed according to the criteria of Bruehl. High and low whole body cooling and warming induced and reduced sympathetic vasoconstrictor activity. The degree of vasoconstrictor activity in both hands was monitored using a videothermograph. The sensitivity and specificity of the calculation methods used to assess the thermographic images were calculated. RESULTS: The temperature difference between the hands in the CRPS patients increases significantly when the sympathetic system is provoked. At both the maximum and minimum vasoconstriction no significant differences were found in fingertip temperatures between both hands. CONCLUSION: The majority of CRPS1 patients do not show maximal obtainable temperature differences between the involved and contralateral extremity at room temperature (static measurement). During cold and warm temperature challenges this temperature difference increases significantly. As a result a higher sensitivity and specificity could be achieved in the diagnosis of CRPS1. These findings suggest that the sympathetic efferent system is involved in CRPS1

Complex regional pain syndrome - phenotypic characteristics and potential biomarkers

Complex regional pain syndrome (CRPS) is a pain condition that usually affects a single limb, often following an injury. The underlying pathophysiology seems to be complex and probably varies between patients. Clinical diagnosis is based on internationally agreed-upon criteria, which consider the reported symptoms, presence of signs and exclusion of alternative causes. Research into CRPS biomarkers to support patient stratification and improve diagnostic certainty is an important scientific focus, and recent progress in this area provides an opportunity for an up-to-date topical review of measurable disease-predictive, diagnostic and prognostic parameters. Clinical and biochemical attributes of CRPS that may aid diagnosis and determination of appropriate treatment are delineated. Findings that predict the development of CRPS and support the diagnosis include trauma-related factors, neurocognitive peculiarities, psychological markers, and local and systemic changes that indicate activation of the immune system. Analysis of signatures of non-coding microRNAs that could predict the treatment response represents a new line of research. Results from the past 5 years of CRPS research indicate that a single marker for CRPS will probably never be found; however, a range of biomarkers might assist in clinical diagnosis and guide prognosis and treatment

Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1

BACKGROUND: In complex regional pain syndrome type 1 (CRPS1) pro-inflammatory mediators and vascular changes play an important role in the sustained development and outcome of the disease. The aim of this study was to determine the involvement of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) during early chronic CRPS1. METHODS: Included were 29 patients with CRPS 1 who were diagnosed during the acute stage of their disease and observed during follow-up visits. Disease activity and impairment were determined and artificial suction blisters were made on the CRPS1 and the contralateral extremities for measurements of IL-6, TNF-α, ET-1 and nitrate/nitrite (NOx). RESULTS: The levels of IL-6, TNF-α and ET-1 in blister fluid in the CRPS1 extremity versus the contralateral extremity were significantly increased and correlated with each other, whereas NOx levels were decreased. CONCLUSION: The NOx/ET-1 ratio appears to be disturbed in the intermediate stage of CRPS, resulting in vasoconstriction and consequently in a diminished tissue blood distribution

Transient Receptor Potential Channel Polymorphisms Are Associated with the Somatosensory Function in Neuropathic Pain Patients

Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p = 0.03), and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V) with cold hypoalgesia (p = 0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p = 0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients

Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

Background. During the chronic stage of Complex Regional Pain Syndrome (CRPS), impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS. Discussion. The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin. Summary. The origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patient's report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients